Organic photoredox catalysts as sustainable and cost-effective replacement forprecious metal complexes in light-driven drug synthesis

项目摘要 该项目开发的基础技术是光氧化还原催化，这是一个活跃的研究领域， 学术界和工业界的兴趣越来越大。光氧化还原催化的影响力有望超过钯 催化，诺贝尔化学奖得主，推动了药物发现的黄金时代。光氧化还原催化 使用光来激活化学反应，而不是传统工艺中的热。唯一单电子 自由基化学是通过光吸收实现新的反应性和前所未有的过程 效率，例如以较少的步骤合成候选药物。此外，由于工业利益，它还允许 在药物开发和生产中使用低成本和结构多样化的原材料， 在常规工艺中不反应。从公共卫生的角度来看，光氧化还原催化具有潜力 通过加速药物治疗， 开发和降低药物制造成本。 完成这个NIH SBIR第二阶段项目将导致高性能有机 光氧化还原催化剂（PC）产品。PC是光氧化还原催化的关键推动者。然而，PC 今天主要使用的是铱和钌，这两种稀有而昂贵的贵金属， 没有超出研发用途的规模，对工业用途造成严重的成本和供应问题。有机PC提供了 溶液它们由丰富的元素制成，具有可持续性，可以轻松扩展以满足工业需求。 值得注意的是，这里感兴趣的有机PC是通过量子模拟设计的，具有临界特性 解决了前几代人的许多局限性。在许多应用中，它们被证明是匹配的，并且在一些应用中， 机箱的性能超过了贵金属PC。这里开发的有机PC提供了可扩展的 用于药物开发和制造所需的光氧化还原催化的解决方案。 具体而言，该项目集成了三个主要组成部分，这些组成部分对于实现工业应用至关重要。 光氧化还原催化，即i）有机PC，ii）光化学反应和iii）光反应器技术。为 有机PC（目标1和2），许多PC候选人将合成扩大范围的反应性 能够适应多种工业反应条件。对于光化学反应（目标3和4）， 具有所述客户兴趣的新型和医学重要反应（具有扩展的底物范围）将 使用各种有机PC开发。最后，对于光反应器集成（目标5），商业上 将确定可利用的光反应器设计和相关的反应条件， 有机PC的性能。

PROJECT SUMMARY The underlying technology developed in this project is photoredox catalysis, an active research area with growing academic and industrial interest. The impact of photoredox catalysis is expected to exceed palladium catalysis, the Nobel-prize-winning chemistry that fueled the golden age of drug discovery. Photoredox catalysis uses light to activate chemical reactions, as opposed to heat in conventional processes. Unique single-electron radical chemistry is accessed through light absorption enabling new reactivities and unprecedented process efficiencies e.g. synthesis of drug candidates in fewer steps. Of additional industrial interest, it also permits the use of low-cost and structurally diverse raw materials in drug development and manufacturing that are otherwise unreactive in conventional processes. From a public health perspective, photoredox catalysis has the potential to substantially lower the cost of therapeutics and improve overall human health by enabling accelerated drug development and reduced drug manufacturing costs. Completing this NIH SBIR Phase II project will result in the commercialization of high performance organic photoredox catalyst (PC) products. PCs are the key enabler of photoredox catalysis. However, PCs predominantly used today are based on iridium and ruthenium, two rare and expensive precious metals that do not scale beyond R&D usage, posing serious cost and supply issues for industrial use. Organic PCs provide the solution. Made from abundant elements, they are sustainable and can easily scale to meet industrial demand. Notably, the organic PCs of interest here were designed by quantum simulations to possess critical properties resolving many limitations of earlier generations. In many applications, they were shown to match and in some cases exceed the performance of precious metal PCs. The organic PCs developed here provide the scalable solution for photoredox catalysis required for drug development and manufacturing. Specifically, this project integrates three main components pivotal to enabling industrial application of photoredox catalysis, namely i) organic PCs, ii) photochemical reactions, and iii) photoreactor technology. For organic PCs (Aims 1 and 2), a number of PC candidates will be synthesized with expanded ranges of reactivities capable of accommodating many industrial reaction conditions. For photochemical reactions (Aims 3 and 4), novel and medicinally important reactions (with extended substrate scope) with stated customer interest will be developed using various classes of organic PCs. Finally, for photoreactor integration (Aim 5), commercially available photoreactor designs and associated reaction conditions will be identified that maximize the performance of organic PCs.